Production device, system, and method

ABSTRACT

To facilitate production of “regenerative medicine products” using a quality by design (QbD) approach.In one embodiment of the present invention, a production device which produces a medical product and analyzes a starting material and a central management device which determines processing conditions in the production device are provided separately. In addition, by transmitting and receiving data and the like pertaining to the starting material between the production device and central management device data, the medical product is produced while production conditions therefor are continuously optimized. Thus, it is easy to produce a medical product while reducing or eliminating effects from changes in cells and tissues over time, from oscillation during transport, and from changes in surrounding environment such as changes in temperature, and to produce the desired medical product even when there are individual differences in the starting material.

TECHNICAL FIELD

The present invention relates to a production device, a system, and amethod. For example, one embodiment of the present invention relates toa production device, a system, and a method for producing a product thatis used for processing human or animal cells or tissues, forreconstructing, repairing, or forming a structure or a function of abody, or for treating or preventing diseases.

BACKGROUND ART

In Japan, it is often necessary to conduct mass and long-termnon-clinical and clinical trials (clinical trials) in order to receivepharmaceuticals approval. Therefore, even when an effectivepharmaceuticals is invented, patients often have to wait for approval.

In 2014, Japanese Pharmaceutical Affairs Law was revised. As a result ofthe revision, a new category of “regenerative medicine products” wasestablished in the Pharmaceutical Affairs Law. For “regenerativemedicine products” newly introduced, if safety is confirmed and efficacyis estimated, a conditional approval system that can be approved earlyhas been introduced. As a result, it is highly likely to provide newtherapeutic agents for various diseases at an early stage.

Among the “regenerative medicine products”, products usingmicroorganism-derived cells or tissues as starting materials are largelyclassified into “autologous products” and “allogeneic products”. The“autologous products” are those that are produced by processing thestarting material collected from a patient and used by the same patient.The “allogeneic products” are those that are produced by processing astarting material collected from a healthy person (different from apatient) and are used by the patient. There are individual differencesin cells or tissues, and performance and quality of the cells or tissuescan change over time, change due to external forces such as oscillationaccompanying during transport, or change from changes in surroundingenvironment. Therefore, it is impossible or extremely difficult toprepare a large amount of starting material with uniform performance andquality. In addition, when the starting material is not uniform, it isdifficult to set appropriate production conditions. Thus, when a process(for example, cell cultivation) that showed good results at the researchstage (small or proprietary production) is diverted to a commercialstage (mass or general-purpose production), similarly, good results arenot always shown. In the worst case, the performance and quality of thecells or tissues may deviate during the process, and thus there is apossibility that the “regenerative medicine products” cannot beproduced.

In order to establish a production process of the “regenerative medicineproducts”, there has been proposed a quality-by-design (QbD) approach(see Non Patent Literature 1). The QbD approach is a pharmaceuticalsquality management approach based on scientific knowledge and riskmanagement (see operation guideline Q8 (formulation development), Q9(quality risk management), and Q10 (pharmaceuticals quality system) formaintaining safety and quality defined in International Council forHarmonisation of Technical Requirements for Pharmaceuticals for HumanUse: ICH).

In short, in the QbD approach, the production process is systematicallymanaged in the following order.

(I) Set quality target product profile (QTPP) of a final product andcritical quality attribute (CQA) of the final product that has a stronginfluence on the QTPP.

(II) Specify critical process parameter (CPP) that affect theperformance and quality of the final product based on risk assessmentand multivariate experiment.

(III) Define the range (hereinafter, referred to as “design space”) ofthe CQA and the CPP required to secure QTPP.

In this specification, the QTPP is a product design standard. That is,the QTPP means a summary of the expected quality characteristics offormulation that should be achieved to ensure the required quality whenconsidering the safety and effectiveness of the formulation. Inaddition, the CQA means physical, chemical, biological, microbiologicalcharacteristics or properties that should be within appropriate limits,ranges, and distributions to ensure the required product quality. Inaddition, the CPP means parameters whose variations affect the CQA andtherefore parameters that should be monitored or managed to ensure thatthe quality required in the process is obtained, among the processparameters.

CITATION LIST Non Patent Literature

-   Non Patent Literature 1: Yonatan Y Lipsitz and 2 other authors,    “Quality cell therapy manufacturing by design”, nature    biotechnology, April 2016, Volume 34, Issue 4, p. 393-400

SUMMARY OF INVENTION Technical Problem

As described above, it is impossible or extremely difficult to prepare alarge amount of starting materials (cells or tissues) with uniformperformance and quality, and as a result, it is not easy to apply a QbDapproach to “regenerative medicine products”. Thus, one embodiment ofthe present invention is to facilitate production of “regenerativemedicine products” using a QbD approach.

Solution to Problem

In one embodiment of the present invention, a production device thatperforms production of a medical product, analyzes a starting material,and the like, and a central management device that determines processingconditions in the production device are provided separately. Inaddition, the medical product is produced by transmitting and receivingdata and the like pertaining to the starting material between theproduction device and central management device data.

For example, according to one embodiment of the present invention, aproduction device includes an analysis unit that generates initialanalysis data of human or animal cell or tissue that is a startingmaterial of a medical product, a communication unit that transmits theinitial analysis data to a central management device and receivesinitial processing data indicating the processing condition of thestarting material optimized by the central management device based onthe initial analysis data within a range of a predetermined design spaceas the processing condition of the starting material, and a processingunit that processes the starting material according to the initialprocessing data.

According to another embodiment of the present invention, a method forproducing a medical product in a production device controlled by acentral management device includes generating, by the production device,initial analysis data of human or animal cell that is a startingmaterial of the medical product, transmitting, by the production device,the initial analysis data to the central management device, generating,by the central management device, initial processing data indicating aprocessing condition of the starting material optimized based on theinitial analysis data within a range of a predetermined design space asa processing condition of the starting material, transmitting, by thecentral management device, the initial processing data to the productiondevice, and processing, by the production device, the starting materialaccording to the initial processing data.

Advantageous Effects of Invention

In one embodiment of the present invention, the production device thatperforms the production of the medical product, analyzes the startingmaterial, and the like, and the central management device thatdetermines the processing conditions in the production device areprovided separately. Thereby, it becomes possible to produce the medicalproduct (on-site production) at the place where the cells or tissueswhich are the starting materials are collected. As a result, it is easyto produce the medical product while reducing or eliminating effectsfrom changes in cells and tissues over time, from oscillation duringtransport, and from changes in surrounding environment such as changesin temperature. In addition, the medical product can also be producednear the patient using the medical product. As a result, it is easy toprovide the medical product to the patient while reducing or eliminatingeffects from the change in the cells and tissues constituting themedical product over time, from the oscillation during transport, andfrom the change in the surrounding environment such as the change intemperature.

In addition, in the embodiment of the present invention, the medicalproduct is produced by transmitting and receiving the data and the likepertaining to the starting material between the production device andthe central management device data. Thereby, it possible to determinethe processing conditions of the starting material based on theperformance and quality of the starting material itself. As a result,even when there are individual differences in the starting material, itbecomes easy to produce the desired medical product.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 is a diagram showing an example of a system according to oneembodiment of the present invention.

FIG. 2 is a diagram showing an example of components of a productiondevice shown in FIG. 1 .

FIG. 3 is a diagram showing an example of functional units of theproduction device shown in FIG. 1 .

FIG. 4 is a diagram showing an example of components of a centralmanagement device shown in FIG. 1 .

FIG. 5 is a diagram showing an example of functional units of thecentral management device shown in FIG. 1 .

FIG. 6 is a diagram showing an example of a sequence of a system shownin FIG. 1 .

FIG. 7 is a diagram showing an example of the sequence of the systemshown in FIG. 1 .

FIG. 8 is a diagram showing an example of the sequence of the systemshown in FIG. 1 .

FIG. 9 is a diagram showing an example of the sequence of the systemshown in FIG. 1 .

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

1. Configuration of System

FIG. 1 is a diagram showing an example of a system according to oneembodiment of the present invention. The system shown in FIG. 1 includesa plurality of production devices 10 and a central management device 20that can communicate with each of the plurality of production devices 10via a network. Note that the network may be constructed by either awired connection or a wireless connection, or a part thereof may beconstructed by the wired connection and the remaining part thereof maybe constructed by the wireless connection.

Each of the production device 10 and the central management device 20shown in FIG. 1 may be installed anywhere as long as the communicationis possible via the network. For example, the production device 10 canbe installed in a medical institution such as a hospital, a clinic, or apharmacy, and the central management device 20 can be installed in acorporate head office or the like.

(1) Production Device

FIG. 2 is a diagram showing an example of components of the productiondevice 10 shown in FIG. 1 . The production device 10 shown in FIG. 2includes a central processing unit (CPU) 101, a line termination device102, a storage device 103, an input/output device 104, an analysisdevice 105, and a processing device 106. These components areelectrically connected to each other via a bus 107. Note that theproduction device of one embodiment of the present invention is notlimited to those including only the components of the production device10 shown in FIG. 2 . For example, in addition to the components shown inFIG. 2 , the production device of one embodiment of the presentinvention may include a transfer device (for example, robot arm) thattransfers a starting material, an intermediate product, or a medicalproduct, which is disposed inside one of the analysis device 105 and theprocessing device 106, to an inside of the other of the analysis device105 and the processing device 106.

The central processing unit (CPU) 101 is used to execute an instructionincluded in software stored in the storage device 103. Specifically, thecentral processing unit (CPU) 101 is used for generation of a signalincluding various types of information transmitted to the centralmanagement device 20, calculation processing based on an operation (ofan input device) of the input/output device 104 by an operator andcontrol (of an output device) of the input/output device 104 forpresenting specific information to the operator, analysis of human oranimal cells or tissues which are starting materials of a medicalproduct, control of the analysis device 105 for performing analysis ofintermediate product obtained by processing the starting materialsand/or analysis of the medical product, control of the processing device106 for processing the starting materials and/or the intermediateproduct, and the like.

The line termination device 102 is used to transmit various signalsgenerated by the central processing unit (CPU) 101 to the centralmanagement device 20, and receive a signal including the processingconditions of the starting material transmitted by the centralmanagement device 20 and/or a signal including the processing conditionsof the intermediate product. Examples of the line termination device 102include a modem, an optical line termination device (ONU), and the like.

The storage device 103 is used to store software including instructionsexecuted by the central processing unit 101 and various data generatedby the central processing unit 101. Examples of the storage device 103include a dynamic random access memory (DRAM), a static random accessmemory (SRAM), a hard disk drive (HDD), and/or a flash memory, acombination thereof, or the like. Further, the storage device 103 mayinclude a volatile storage unit including a DRAM and the like, and anonvolatile storage unit including an HDD and the like. In this case,for example, the nonvolatile storage unit can be used to store softwareincluding instructions to be executed by the central processing unit101, and the volatile storage unit can be used to temporarily storevarious data generated by the central processing unit 101.

The input/output device 104 is used for an operator to operate theproduction device 10 and to present information to the operator.Examples of the input/output device 104 include a touch panel and thelike. Further, the input/output device 104 may be separated into aninput device and an output device. Examples of the input device includea pointing device such as a touchpad and a mouse, a keyboard, a button,and a microphone, a combination thereof, or the like. In addition,examples of the output device include a display (monitor) and a speaker,or a combination thereof.

The analysis device 105 is used to analyze human or animal cells ortissues which are starting materials of a medical product, anintermediate product and a medical product obtained by processing thestarting materials, and body fluids such as blood and saliva, body hairsuch as hair, nails, and the like that are collected from a human or ananimal providing the starting materials. Examples of the analysis device105 include a freeze drying device, a sample collection device, a bloodanalysis device, a flow cytometer, a liquid chromatography, a gaschromatography, a mass analysis device, an image analysis device, a cellanalysis device, a gene amplification device, a gene analysis device, anenzyme immunoreactor, a spectrophotometer, an absorptiometer, a weighscale, a thermometer, a densitometer, an osmometer, a pH meter, aphotoelectric sensor, a voltmeter, an ammeter, an imaging device, amicrobial culture device, a microbial analysis device, a nuclearmagnetic resonance device, an X-irradiation device, a computedtomography device, an ultrasonic tomography device, an X-ray imagingdevice, two or more combinations thereof, and the like.

The processing device 106 is used for processing (for example,culturing) the starting material and the intermediate product. Examplesof the processing device 106 include various cell separators thatinclude a freeze drying device, a laser microdissection device, adispersing device, a crushing device, a centrifugal separation(including elutriation) device, a separation device using adhesion ormagnetic bead, a cell sorting device, a gene amplification device, agene introduction device using methods such as an electroporationmethod, a lipofection method, a particle gun method, an ultrasonicmethod, and a virus vector method or using methods not using thesemethods, a gene modification device using a nuclease, a constanttemperature device, a liquid culture medium dialysis device, anadsorption device, a liquid culture medium circulation device, a tracesubstance addition device, a pressurizing and depressurizing device, ashaking device, an oscillation generation device, an ultrasonicgeneration device, a magnetic field generation device, a programfreezing device, a cell thawing device, a heating device, a coolingdevice, an aseptic filling device, an aseptic maintenance device, an airconditioner and a radiation irradiation device, two or more combinationsthereof, and the like.

FIG. 3 is a diagram showing an example of functional units of theproduction device 10 shown in FIG. 1 . The production device 10 shown inFIG. 3 includes an input/output unit 121, a storage unit 122, ananalysis unit 123, a communication unit 124, and a processing unit 125.Note that the production device of one embodiment of the presentinvention is not limited to those including only the functional units ofthe production device 10 shown in FIG. 3 . For example, as theproduction device of one embodiment of the present invention, inaddition to the functional units shown in FIG. 3 , a transfer unithaving a function of transferring a starting material, an intermediateproduct, or a medical product to a desired place (for example, from oneof the analysis unit and the processing unit to the other of theanalysis unit and the processing unit) may be provided inside theproduction device 10.

The input/output unit 121 includes a function of receiving instructionsand the like pertaining to production of a medical product from theoperator, and presenting information pertaining to the production of themedical product to the operator. For example, the input/output unit 121may include a function of presenting to an operator that a medicalproduct is not currently being produced in the production device 10,presenting an option as to whether or not to start the production of themedical product, and receiving the instruction when the operator selectsthat the production of the medical product starts. Note that thefunction of the input/output unit 121 is implemented by the centralprocessing unit 101, the input/output device 104, and the like shown inFIG. 2 .

The storage unit 122 has a function of storing data necessary forproducing the medical product and updating existing data. For example,the storage unit 122 may include a function of storing analysis dataobtained by analyzing the starting material, the intermediate product,and the medical product and processing data indicating processingconditions of the starting material and the intermediate producttransmitted from the central management device 20, and updating a signalfor changing conditions when these analyses are performed and/or asignal for changing a design space set in a particular productionprocess when the signals are transmitted from the central managementdevice 20. Note that the function of the storage unit 122 is implementedby the central processing unit 101, the storage device 104, and the likeshown in FIG. 2 .

The analysis unit 123 includes a function of analyzing the startingmaterial, the intermediate product, and the medical product (referred toas “starting material and the like” in this paragraph). For example, theanalysis unit 123 may include a function of analyzing at least one ofsizes, color tones, weights, cell particle sizes, expression rates ofvarious cell surface antigens, the amount of various gene expressions,the number of viable cells, viable cell rates, and expressed genes ofcells or tissues constituting starting materials and the like, andpathogenic microorganisms and proliferating viruses included in thestarting material and the like. In addition, the analysis unit 123 mayinclude a function of analyzing at least one of properties,compositions, drug concentrations, and genes of cells or tissuesconstituting body fluids such as blood and saliva, body hairs such ashair, nails, and the like (referred to as “body fluid and the like” inthis paragraph), and proliferating viruses included in the body fluidand the like. Note that the function of the analysis unit 123 isimplemented by the central processing unit 101, the analysis device 105,and the like shown in FIG. 2 .

The communication unit 124 has a function of transmitting a signal tothe central management device 20 and receiving a signal transmitted bythe central management device 20. For example, the communication unit124 may include a function of transmitting a signal indicating theanalysis result of the starting material and a signal requesting toteach optimal processing conditions for the signal, and also receiving asignal indicating the processing conditions of the starting materialtransmitted by the central management device 20. Note that the functionof the communication unit 124 is implemented by the central processingunit 101, the line termination device 102, and the like shown in FIG. 2.

The processing unit 125 includes a function of processing the startingmaterial and/or the intermediate product according to the processingconditions transmitted from the central management device 20. Forexample, the processing unit 125 may include a function of processinghuman or animal cells or tissues which are starting materials orintermediate products (specifically, dispersion of tissue, crushing,laser microdissection, centrifugation (including elutriation), variouscell separation including adhesion or separation using magnetic bead,introduction of genes using methods such as an electroporation method, alipofection method, a particle gun method, an ultrasonic method, and avirus vector method or using methods not using these methods,modification of genes using various nucleases, cultivation,pressurization/depressurization, shaking, oscillation irradiation,ultrasonic irradiation, magnetic field generation, freezing, thawing,heating, cooling, replacing all or part of media, adjustment of asurface area in a culture vessel, control of a cell concentration byadjusting the amount of medium, control of temperature, illumination,oscillation, current, magnetic field, barometric pressure, andatmosphere, addition of solvents or additives, aseptic filling, and thelike), and modifying the ability. Note that the function of theprocessing unit 125 is implemented by the central processing unit 101,the processing device 106, and the like shown in FIG. 2 .

(2) Central Management Device

FIG. 4 is a diagram showing an example of components of the centralmanagement device 20 shown in FIG. 1 . The central management device 20shown in FIG. 4 includes a central processing unit (CPU) 201, a linetermination device 202, a storage device 203, an input/output device204, and a parallel processing device 205. These components areelectrically connected to each other via a bus 206. Note that theproduction device of one embodiment of the present invention is notlimited to those including only the components of the central managementdevice 20 shown in FIG. 4 . For example, in addition to the componentsshown in FIG. 4 , the central management device of one embodiment of thepresent invention may experimentally include devices similar to theanalysis device 105 and the processing device 106 included in theproduction device 10.

The central processing unit (CPU) 201 is used to execute an instruction(excluding those executed by the parallel processing device 205)included in software stored in the storage device 203. Specifically, thecentral processing unit (CPU) 201 is used to perform generation ofsignals (excluding those generated by the parallel processing device205) including various information transmitted to the production device10 and calculation processing based on the operation (of the inputdevice) of the input/output device 204 by the operator and control (ofthe output device) of the input/output device 204 for presentingspecific information to the operator.

The line termination device 202 is used to transmit various signalsgenerated by the central processing unit (CPU) 201 and the parallelprocessing device 205 to the production device 10, and receive a signalindicating an analysis result of the starting material transmitted bythe production device 10 and/or a signal indicating an analysis resultof the intermediate product. Examples of the line termination device 202include a modem, an optical line termination device (ONU), and the like.

The storage device 203 is used to store software including instructionsexecuted by the central processing unit 201 and the parallel processingdevice 205 and various data generated by the central processing unit 201and the parallel processing device 205. Examples of the storage device203 include a DRAM, an SRAM, an HDD and/or a flash memory, a combinationthereof, or the like. Further, the storage device 203 may include avolatile storage unit including a DRAM and the like, and a nonvolatilestorage unit including an HDD and the like. In this case, for example,the nonvolatile storage unit can be used to store software includinginstructions to be executed by the central processing unit 201, and thevolatile storage unit can be used to temporarily store various datagenerated by the central processing unit 201.

The input/output device 204 is used for an operator to operate thecentral management device 20 and to present information to the operator.Examples of the input/output device 204 include a touch panel and thelike. Further, the input/output device 204 may be separated into aninput device and an output device. Examples of the input device includea pointing device such as a touchpad and a mouse, a keyboard, a button,and a microphone, a combination thereof, or the like. In addition,examples of the output device include a display (monitor) and a speaker,or a combination thereof.

The parallel processing device 205 is used to execute an instruction(excluding those executed by the central processing unit 201) includedin software stored in the storage device 203. For example, the parallelprocessing device 205 is used to determine the optimal processingconditions for the starting material or the intermediate product basedon the analysis result of the starting material or the intermediateproduct transmitted from the production device 10 within a predetermineddesign space, and furthermore, perform machine learning using theanalysis results of the starting material, the intermediate product, andthe medical product as data.

FIG. 5 is a diagram showing an example of functional units of thecentral management device 20 shown in FIG. 1 . The central managementdevice 20 shown in FIG. 5 includes an input/output unit 221, a storageunit 222, an analysis unit 223, and a communication unit 224. Note thatthe central management device of one embodiment of the present inventionis not limited to those including only the functional units of thecentral management device 20 shown in FIG. 5 . For example, the insideof the central management device 20 as the central management device ofone embodiment of the present invention may be provided with an analysisunit that includes a function of analyzing samples of the startingmaterial, the intermediate product, or the medical product and aprocessing unit that includes a function of processing samples of thestarting material and the intermediate product, in addition to thefunctional units shown in FIG. 5 .

The input/output unit 221 includes a function of receiving instructionsand the like pertaining to production of a medical product from theoperator, and presenting information pertaining to the production of themedical product to the operator. For example, the input/output unit 221may include a function of presenting the operator with an option tochange the design space of a specific production process as a result ofmachine learning by the parallel processing device 205, and furthermore,receiving an instruction to change the design space of the specificproduction process by the operator. Note that the function of theinput/output unit 221 is implemented by the central processing unit 201,the input/output device 204, and the like shown in FIG. 4 .

The storage unit 222 includes a function of storing data necessary forproducing the medical product and updating existing data. For example,the storage unit 222 may include a function of storing the analysis dataof the starting material, the intermediate product, and the medicalproduct transmitted from a plurality of production devices 10 so far andthe processing data indicating the processing conditions of the startingmaterial and the intermediate product determined using the parallelprocessing device 205, and furthermore, updating an instruction forchanging the design space of the specific production process when theinstruction is received from the operator. Note that the function of thestorage unit 222 is implemented by the central processing unit 201, thestorage device 204, and the like shown in FIG. 4 .

The analysis unit 223 includes a function of deriving the optimalprocessing conditions for the starting material or the intermediateproduct. For example, the analysis unit 223 includes a function ofdetermining the processing conditions when the signal indicating theanalysis result of the starting material or the intermediate product istransmitted from the production device 10 and furthermore, performingmachine learning on the analysis data of the starting material or theintermediate product, the processing data therefor, and the resultinganalysis data of the medical product as data. Note that the function ofthe analysis unit 223 is implemented by the parallel processing device205 and the like shown in FIG. 4 .

The communication unit 224 has a function of transmitting a signal tothe production device 10 and receiving a signal transmitted by theproduction device 10. For example, the communication unit 224 mayinclude a function of transmitting a signal indicating the processingconditions of the starting material and a signal indicating that thestarting material is processed accordingly to the production device 10,and furthermore, receiving a signal indicating the analysis result ofthe starting material transmitted by the production device 10. Note thatthe function of the communication unit 224 is implemented by the centralprocessing unit 201, the termination device 202, and the like shown inFIG. 2 .

2. Sequence of System

FIGS. 6 to 9 are diagrams showing an example of a sequence of a systemshown in FIG. 1 . Hereinafter, each sequence will be described indetail.

(1) As to Sequence Shown in FIG. 6

First, in the production device 10, the analysis of the human or animalcells or tissues, which are the starting materials of the medicalproduct, is performed (S11). Note that examples of the analysis mayinclude measurement of a size, a color tone, a weight, a cell particlesize, expression rates of various cell surface antigen, the amount ofvarious gene expression, the number of viable cells, or a viable cellrate of human or animal cell or tissue which is the starting material,and qualitative and quantitative determination of expressed gene orexpressed protein, measurement of drug concentration of the startingmaterial, detection and identification of pathogenic microorganisms orproliferating viruses included in the starting material, and the like.The production device 10 transmits the signal (initial analysis data)indicating the analysis result of the starting material to the centralmanagement device 20.

Next, in the central management device 20, the processing conditions ofthe starting material are determined based on the initial analysis data(S21). Note that the processing conditions are determined within thepredetermined design space. The central management device 20 transmitsthe signal (initial processing data) indicating the processingconditions of the starting material to the production device 10.

Next, in the production device 10, the starting material is processedbased on the initial processing data (S12). Examples of the processingincludes drying, immersion, dispersion, crushing, centrifugation(including elutriation), various cell separations including adhesion orseparation using magnetic bead, introduction of gene using methods suchas an electroporation method, a lipofection method, a particle gunmethod, an ultrasonic method, and a virus vector method or methods notusing these methods, modification of genes using various nucleases,cultivation, pressurization/depressurization, shaking, oscillationirradiation, ultrasonic irradiation, magnetic field generation,freezing, thawing, heating, cooling, replacing all or part of media,adjustment of a surface area in a culture vessel, control of a cellconcentration by adjusting the amount of medium, control of temperature,illumination, oscillation, current, magnetic field, barometric pressure,and atmosphere, addition of solvents or additives, aseptic filling, andthe like.

In the sequence shown in FIG. 6 , the medical product is completed bythe above process (S13).

In the sequence shown in FIG. 6 , the separately provided productiondevice 10 and the production device 10 separately provided from thecentral management device 20 for determining processing conditionsproduce a medical product. Thereby, the degree of freedom of theproduction place of the medical product is increased. As a result, it iseasy to produce the medical product while reducing or eliminatingeffects from the change in the human or animal cells and tissues, whichare the starting materials, over time, from the oscillation duringtransport, and from the change in the surrounding environment such aschanges in temperature. In addition, the medical product can also beproduced near the patient using the medical product. As a result, it iseasy to provide the medical product to the patient while reducing oreliminating effects from the change in the cells and tissuesconstituting the medical product over time, from the oscillation duringtransport, and from the change in the surrounding environment such asthe change in temperature.

In addition, in the sequence shown in FIG. 6 , the processing conditionsof the starting material are determined based on the analysis result ofthe starting material. As a result, it is easy to set the optimalprocessing conditions for the starting material. As a result, even whenthere are individual differences in the starting material, it becomeseasy to produce the desired medical product.

Note that the medical product produced by the sequence shown in FIG. 6may be either “autologous product” or “allogeneic product”. However,when the medical product is the “autologous product”, there is apossibility that the quality of cells or tissues (starting materials)collected from a patient may vary greatly depending on the disease stateor condition. Even in such a case, in the sequence shown in FIG. 6 ,since the processing conditions are determined based on the analysisdata of the starting material, the medical product can be produced withhigh accuracy.

(2) As to the Sequence Shown in FIG. 7

First, in the production device 10, not only the analysis (hereinafterreferred to as “the former analysis”) of the human or animal cells ortissues which are the starting materials of the medical product, butalso the analysis (hereinafter, referred to as “the latter analysis”)body fluids such as blood and saliva collected from human or animalsthat have provided the starting material, body hair such as hair, nails,and the like (referred to as “body fluid and the like” in thisparagraph) is performed (S14). Examples of the former analysis includeat least one of measurement of sizes, color tones, weights, cellparticle sizes, expression rates of various cell surface antigens, theamount of various gene expressions, the number of viable cells, orviable cell rates of cells or tissues, analysis of expressed gene,detection and identification of pathogenic microorganisms included inthe starting material, and detection and identification of proliferatingviruses. In addition, examples of the latter analysis include at leastone of analysis of properties, compositions, drug concentration, genes,and the like of cells or tissues, and detection and identification ofproliferating viruses included in body fluids, and the like. Theproduction device 10 transmits a signal (initial analysis data)indicating the former analysis result and a signal (clinical data)indicating the latter analysis result to the central management device20.

Next, in the central management device 20, the processing conditions ofthe starting material are determined based on the initial analysis dataand the clinical data (S22). Note that the processing conditions aredetermined within the predetermined design space. The central managementdevice 20 transmits the signal (initial processing data) indicating theprocessing conditions to the production device 10.

Next, in the sequence shown in FIG. 7 , the same process as the sequenceshown in FIG. 6 is performed (S12), and thus the medical product iscompleted (S13).

The sequence shown in FIG. 7 has the same advantages as the sequenceshown in FIG. 6 . In addition, the medical product produced by thesequence shown in FIG. 7 may be either “autologous product” or“allogeneic product”. When the medical product is the “autologousproduct”, the sequence shown in FIG. 7 has the above-describedadvantages.

Further, in the sequence shown in FIG. 7 , the processing conditions ofthe starting material are determined based not only on the analysisresult of the starting material, but also on body fluids of human oranimals that have provided the starting material, and the like. As aresult, it is easy to set the optimal processing conditions for thestarting material. As a result, even when there are individualdifferences in the starting material, it becomes easy to produce thedesired medical product.

(3) As to the Sequence Shown in FIG. 8

First, the same processes as the sequence shown in FIG. 6 are performed(S11, S21, and S12), and thus the intermediate product is generated(S15).

Next, the analysis of the intermediate product is performed (S15).Examples of the analysis include at least one of measurement of thenumber of viable cells or a viable cell rate in the intermediateproduct, analysis of cell surface antigens, analysis of variousexpressed genes, analysis of the amount of various expressed genes,concentration of substances in a culture solution, and detection andidentification of pathogenic microorganisms included in the intermediateproduct, and detection and identification of proliferating viruses, andthe like. The production device 10 transmits the signal (initialanalysis data) indicating the analysis result of the intermediateproduct to the central management device 20.

Next, in the central management device 20, the processing conditions ofthe intermediate product are determined based on the intermediateanalysis data (S23). Note that the processing conditions are determinedwithin the predetermined design space. The central management device 20transmits the signal (intermediate processing data) indicating theprocessing conditions of the intermediate product to the productiondevice 10.

Next, in the production device 10, the intermediate product is processedbased on the initial processing data (S17). Examples of the processingincludes drying, immersion, dispersion, crushing, centrifugation(including elutriation), various cell separations including adhesion orseparation using magnetic bead, introduction of gene using methods suchas an electroporation method, a lipofection method, a particle gunmethod, an ultrasonic method, and a virus vector method or methods notusing these methods, modification of genes using various nucleases,cultivation, pressurization/depressurization, shaking, oscillationirradiation, ultrasonic irradiation, magnetic field generation,freezing, thawing, heating, cooling, replacing all or part of media,adjustment of a surface area in a culture vessel, control of a cellconcentration by adjusting the amount of medium, control of temperature,illumination, oscillation, current, magnetic field, barometric pressure,and atmosphere, addition of solvents or additives, aseptic filling, andthe like.

In the sequence shown in FIG. 8 , the medical product is completed bythe above process (S13).

The sequence shown in FIG. 8 has the same advantages as the sequenceshown in FIG. 6 . In addition, the medical product produced by thesequence shown in FIG. 8 may be either “autologous product” or“allogeneic product”. When the medical product is the “autologousproduct”, the sequence shown in FIG. 8 has the above-describedadvantages.

Further, in the sequence shown in FIG. 8 , the production process of themedical product is determined based not only on the analysis result ofthe starting material but also the analysis result of the intermediatematerial. As a result, it possible to set the optimal processingconditions for the intermediate product. As a result, it is possible toreduce the probability that the performance and quality of theintermediate product deviate during the production process.

(4) As to the Sequence Shown in FIG. 9

First, the same process as the sequence shown in FIG. 6 is performed(S11, S21, and S12), and thus the medical product is completed (S13).

Next, the analysis of the medical product is performed (S17). Example ofthe analysis includes at least one of measurement of the number ofviable cells or a viable cell rate in the medical product, analysis ofcell surface antigens, analysis of various expressed genes, analysis ofthe amount of various expressed genes, analysis of various cellfunctions, measurement of concentration of substances in a solvent,measurement of osmotic pressure, analysis of morphology and particlesize of cell and distribution thereof, analysis of a color tone,measurement of a weight, detection and identification of pathogenicmicroorganisms included in the medical product, detection andidentification of proliferating viruses, and the like. The productiondevice 10 transmits the signal (final analysis data) indicating theanalysis result of the medical product to the central management device20.

Next, in the central management device 20, the initial analysis data,the initial processing data, and the final analysis data received orgenerated in this sequence are stored in association with each other(S24). These newly stored data are used as data for machine learning inthe central management device 20 (S25).

The sequence shown in FIG. 9 has the same advantages as the sequenceshown in FIG. 6 . In addition, the medical product produced by thesequence shown in FIG. 9 may be either “autologous product” or“allogeneic product”. When the medical product is the “autologousproduct”, the sequence shown in FIG. 9 has the above-describedadvantages.

Further, in the sequence shown in FIG. 9 , the central management device20 uses the newly obtained analysis data and processing data as themachine learning data. As a result, it possible to improve the accuracyof processing conditions determined by the central management device 20in proportion to the number of analysis data and processing data storedin the central management device 20. As a result, it is possible toreduce the probability that the performance and quality of the human oranimal cells or tissues which are the starting materials deviate duringthe production process.

(5) As to Modifications

A sequence of a system of one embodiment of the present invention is notlimited to the sequences shown in any of FIGS. 6 to 9 . For example, asequence for performing all of the processes (S11 to S17 and S21 to 25)shown in FIGS. 6 to 9 is also included in the sequence of the systemaccording to one embodiment of the present invention. Further, theprocesses (S16, S23, and S17) related to the analysis and processing ofthe intermediate product shown in FIG. 8 can be performed a plurality oftimes.

What is claimed is:
 1. A system including a plurality of productiondevices, each of the production devices comprising: an analysis unitthat measures data corresponding to a viable cell rate of a startingmaterial of a medical product; a communication unit that transmits themeasured data to a central management device via a network constructedby either a wired connection or a wireless connection and receivesinitial processing data indicating a processing condition of thestarting material optimized by the central management device based onthe measured data within a range of a predetermined design space as theprocessing condition of the starting material; and a processing unitthat processes the starting material according to the initial processingdata to produce the medical product, wherein the central managementdevice and the production device are separately provided, and whereinthe central management device does not comprise the processing unit,wherein the analysis unit generates final analysis data of the medicalproduct produced from the starting material, and the communication unittransmits the final analysis data to the central management device torecord the final analysis data by associating the final analysis datawith the measured data and the initial processing data in the centralmanagement device, and wherein the central management device comprises:a central storage unit that records the measured data, the initialprocessing data, and the final analysis data transmitted from each ofthe plurality of production devices in association with each other; acentral analysis unit that, in response to a target production device ofthe plurality of production devices transmitting latest measured datanewly generated by the target production device, generates latestinitial processing data optimal for the latest measured data byreferring to the measured data, the initial processing data, and thefinal analysis data recorded in association with each other in thecentral storage unit; and a central communication unit that transmitsthe latest initial processing data to the target production device. 2.The production device according to claim 1, wherein the analysis unitgenerates intermediate analysis data of the intermediate productobtained by processing the starting material, the communication unittransmits the intermediate analysis data to the central managementdevice and receives intermediate processing data indicating theprocessing condition of the intermediate product optimized by thecentral management device based on the intermediate analysis data withina range of a predetermined design space as the processing condition ofthe intermediate product, and the processing unit processes theintermediate product according to the intermediate processing data. 3.The production device according to claim 1, wherein the processing unitcultivates the cell or tissue.
 4. The production device according toclaim 1, further comprising: a transfer unit that transfers the startingmaterial from one of the analysis unit and the processing unit to theother of the analysis unit and the processing unit.
 5. The productiondevice according to claim 1, wherein the medical product is anautologous product.
 6. The system according to claim 1, wherein thecommunication unit directly transmits the measured data to the centralmanagement device.
 7. The system according to claim 1, and wherein theanalysis unit, the communication unit, and the processing unit are localto a collection site of the starting material and the central managementdevice is remote to the collection site of the starting material.
 8. Asystem including a plurality of production devices, each of theproduction devices comprising: an analysis unit that measures datacorresponding to a viable cell rate of a starting material of a medicalproduct and a clinical data of the human or animal; a communication unitthat transmits the measured data to a central management device via anetwork constructed by either a wired connection or a wirelessconnection and receives initial processing data indicating a processingcondition of the starting material optimized by the central managementdevice based on the measured data within a range of a predetermineddesign space as the processing condition of the starting material; and aprocessing unit that processes the starting material according to theinitial processing data to produce the medical product, wherein thecentral management device and the production device are separatelyprovided, and wherein the central management device does not comprisethe processing unit, wherein the analysis unit generates final analysisdata of the medical product produced from the starting material, and thecommunication unit transmits the final analysis data to the centralmanagement device to record the final analysis data by associating thefinal analysis data with the measured data and the initial processingdata in the central management device, and wherein the centralmanagement device comprises: a central storage unit that records themeasured data, the initial processing data, and the final analysis datatransmitted from each of the plurality of production devices inassociation with each other; a central analysis unit that, in responseto a target production device of the plurality of production devicestransmitting latest measured data newly generated by the targetproduction device, generates latest initial processing data optimal forthe latest measured data by referring to the measured data, the initialprocessing data, and the final analysis data recorded in associationwith each other in the central storage unit; and a central communicationunit that transmits the latest initial processing data to the targetproduction device.
 9. A method for producing a medical product in asystem including a plurality of production devices, each of theproduction devices is controlled by a central management device, themethod comprising: measuring, by each of the production devices, datacorresponding to a viable cell rate of a starting material of a medicalproduct, and generating final analysis data of the medical productproduced from the starting material; transmitting, by the productiondevice, the measured data to the central management device via a networkconstructed by either a wired connection or a wireless connection;generating, by the central management device, initial processing dataindicating a processing condition of the starting material optimizedbased on the measured data within a range of a predetermined designspace as a processing condition of the starting material; transmittingthe final analysis data to the central management device to record thefinal analysis data by associating the final analysis data with themeasured data and the initial processing data in the central managementdevice; transmitting, by the central management device, the initialprocessing data to the production device; and processing, by theproduction device, the starting material according to the initialprocessing data to produce the medical product, wherein the centralmanagement device and the production device are separately provided,wherein the central management device comprises: a central storage unitthat records the measured data, the initial processing data, and thefinal analysis data transmitted from each of the plurality of productiondevices in association with each other; and a central analysis unitthat, in response to a target production device of the plurality ofproduction devices transmitting latest measured data newly generated bythe target production device, generates latest initial processing dataoptimal for the latest measured data by referring to the measured data,the initial processing data, and the final analysis data recorded inassociation with each other in the central storage unit; and a centralcommunication unit that transmits the latest initial processing data tothe target production device.